1. Field of the Invention
The present invention relates to a vaccine for control of fertility and in particular to a polyvalent vaccine having a multiplicity of determinant antigens in the reproductive system linked to at least one, and preferably more than one, carrier.
2. Description of the Prior Art
The present invention is directed to an active immunological approach for control of fertility by antibodies intercepting the action of one or more gonadotropins. The pituitary luteinizing hormone (LH) and chorionic gonadotropin (CG) exercise a critical role in the regulation of fertility in primates. The former is important for ovulation and steroidogenesis, the latter for rescue of corpus luteum and maintenance of steroidogenesis up to the time of placental shift. Human chorionic gonadotropin (hCG) is an early product of trophoblast and is recognized to be essential for the establishment and sustenance of pregnancy. Both active and passive immunological approaches have been demonstrated to be effective in primates for control of fertility. Use was made in such immunizations of Freunds Complete Adjuvant (C.F.A.) which is unacceptable for eventual human use. The present invention concerns an active polyvalent vaccine which can induce the formation of antibodies in primates effective against both gonadotropins without the use of C.F.A. The vaccine of the present invention leads to the formation of antibodies capable of reacting with the complete hCG molecule consisting of both .alpha. and .beta. subunits to produce neutralization of its biological activity as well as diminish, to an extent, the bioactivity of LH. The vaccine produces antibodies devoid of cross-reactivity with body tissues and the antibody response is of controlled and reasonably long duration, providing an immunity which is reversible, free from toxicity and contra-indications to body functions and also does not cause extra hypersensitivity problems.
The anti-hCG immunization approach of the present invention is known from earlier work and in particular from the inventor's earlier Canadian Patent No. 1,054,937, issued May 22, 1979 and also Canadian Patent No. 1,057,742 (Stevens) issued July 3, 1979. However, these two investigators of anti-hCG vaccines have used fundamentally different approaches. The present inventor has used the .beta. subunit of the hormone hCG, while Stevens has used the 37 amino acid carboxy-terminal peptide (CTP) of the same subunit. The modes by which this "self" protein is rendered immunogenic are also different. The present inventor has utilized a carrier, such as tetanus toxoid, whereas Stevens and co-workers initially advocated haptenic modification of the protein although they subsequently opted for the carrier approach.
hCG is a glycoproteinic hormone composed of two subunits, .alpha. and .beta.. The .alpha. subunit is common to three other pituitary hormones, TSH, LH, and FSH. It is the .beta. subunit which confers in each case the hormonal individuality to these hormones. Thus, the use of only the .beta. subunit of hCG as antigen reduces the chances that the antibodies will cross-react with the other glycoprotein hormones, in particular TSH and FSH. While the female immune system is normally tolerant to hCG and would not be expected to produce antibodies following injection of the hormone, immunogencity can be introduced by modifying the molecule either by attaching haptenic groups or by linking it to an immunogenic "carrier" protein. Thus, in aforementioned Canadian Patent No. 1,054,937 immunization is effected using a vaccine in which .beta.hCG is chemically linked to tetanus toxoid. This vaccine produces antibodies against both the pregnancy hormone hCG as well as tetanus toxoid. However, the efficacy of the vaccine is not adequate for some "low responder" subjects whose antibody response is too low to prevent pregnancy. The marked variation (constitutional variations) in response among subjects indicates a need to modify the vaccine so that adequate antibody response is elicited in the majority, if not all, of recipients.